Anatoly Buchin

Cajal Neuroscience · Human Multiomics

Significance statement: Ion regulation in the brain is a major determinant of neural excitability. Intracellular chloride in neurons, a partial determinant of the resting potential and the inhibitory reversal potentials, is regulated together with extracellular potassium via kation chloride cotransporters. During temporal lobe epilepsy, the homeos...

Gene expression studies suggest that differential ion channel expression contributes to differences in rodent versus human neuronal physiology. We tested whether h-channels more prominently contribute to the physiological properties of human compared to mouse supragranular pyramidal neurons. Single cell/nucleus RNA sequencing revealed ubiquitous HC...

The neocortex is disproportionately expanded in human compared to mouse, both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers that selectively make connections within the cortex and other telencephalic structures. Single-cell transcriptomic analyses of human and mouse cortex show an incr...

Temporal lobe epilepsy is the fourth most common neurological disorder with about 40% of patients not responding to pharmacological treatment. Increased cellular loss in the hippocampus is linked to disease severity and pathological phenotypes such as heightened seizure propensity. While the hippocampus is the target of therapeutic interventions su...

Identifying the cell types constituting brain circuits is a fundamental question in neuroscience and motivates the generation of taxonomies based on electrophysiological, morphological and molecular single cell properties. Establishing the correspondence across data modalities and understanding the underlying principles has proven challenging. Bio-...

The brain consists of many cell classes yet in vivo electrophysiology recordings are typically unable to identify and monitor their activity in the behaving animal. Here, we employed a systematic approach to link cellular, multi-modal in vitro properties from experiments with in vivo recorded units via computational modeling and optotagging experim...

The brain consists of many cell classes yet in vivo electrophysiology recordings are typically unable to identify and monitor their activity in the behaving animal. Here, we employed a systematic approach to link cellular, multi-modal in vitro properties from experiments with in vivo recorded units via computational modeling and optotagging experim...

Temporal lobe epilepsy is the fourth most common neurological disorder, with about 40% of patients not responding to pharmacological treatment. Increased cellular loss is linked to disease severity and pathological phenotypes such as heightened seizure propensity. While the hippocampus is the target of therapeutic interventions, the impact of the d...

Which cell types constitute brain circuits is a fundamental question, but establishing the correspondence across cellular data modalities is challenging. Bio-realistic models allow probing cause-and-effect and linking seemingly disparate modalities. Here, we introduce a computational optimization workflow to generate 9,200 single-neuron models with...

Which cell types constitute brain circuits is a fundamental question, but establishing the correspondence across cellular data modalities is challenging. Bio-realistic models allow probing cause-and-effect and linking seemingly disparate modalities. Here, we introduce a computational optimization workflow to generate 9,200 single-neuron models with...

The neocortex is disproportionately expanded in human compared with mouse1,2, both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers composed of neurons that selectively make connections within the neocortex and with other telencephalic structures. Single-cell transcriptomic analyses of hu...

Temporal lobe epilepsy is the fourth most common neurological disorder with about 40% of patients not responding to pharmacological treatment. Increased cellular loss in the hippocampus is linked to disease severity and pathological phenotypes such as heightened seizure propensity. While the hippocampus is the target of therapeutic interventions su...

Gene expression studies suggest that differential ion channel expression contributes to differences in rodent versus human neuronal physiology. We tested whether h-channels more prominently contribute to the physiological properties of human compared to mouse supragranular pyramidal neurons. Single-cell/nucleus RNA sequencing revealed ubiquitous HC...

Pharmacoresistant epilepsy is a common neurological disorder in which increased neuronal intrinsic excitability and synaptic excitation lead to pathologically synchronous behavior in the brain. In the majority of experimental and theoretical epilepsy models, epilepsy is associated with reduced inhibition in the pathological neural circuits, yet eff...

Pharmacoresistant epilepsy is a common neurological disorder in which increased neuronal intrinsic excitability and synaptic excitation lead to pathologically synchronous behavior in the brain. In the majority of experimental and theoretical epilepsy models, epilepsy is associated with reduced inhibition in the pathological neural circuits, yet eff...

Gene expression studies suggest that differential ion channel expression contributes to differences in rodent versus human neuronal physiology. We tested whether h-channels more prominently contribute to the physiological properties of human compared to mouse supragranular pyramidal neurons. Single- cell/nucleus RNA sequencing revealed ubiquitous H...

Abstract of poster presentation at OCNS-2017

Pharmacoresistant epilepsy is a common neurological disorder in which the basic mechanisms of neuronal excitability and connection processes lead to pathologically synchronous behavior in the brain [1]. In the majority of experimental and theoretical epilepsy models, epilepsy is associated with reduced inhibition in the pathological neural circuits...

• Ion regulation in the brain is a major determinant of neural excitability • Intracellular chloride in neurons is regulated together with extracellular potassium by Kation Chloride Cotransporter 2 (KCC2) • During temporal lobe epilepsy, the regulation of intracellular chloride is impaired in the pyramidal cells due to KCC2(-) pathology • Using rea...

Purkinje neurons play an important role in cerebellar computation since their axons are the only projection from the cerebellar cortex to deeper cerebellar structures. They have com- plex internal dynamics, which allow them to fire spontaneously, display bistability, and also to be involved in network phenomena such as high frequency oscillations a...

History dependence of the ISR curve. A. Current injection of 1 s noise waveform periods in a Purkinje cell in a cerebellar slice, as in Fig 1A. B. Firing frequency vs. noise amplitude σ for five different holding currents Iin. C. Current injection of 1 s noise waveform periods in a different cell with a more pronounced bistability. The firing frequ...

ISR and dendrite filtering. A. Experimental determination of dendritic filtering properties. Voltage response of a Purkinje cell (black) to a short current pulse (0.5 ms, 1 nA), fitted with a biexponential function with time constants τm and τc (red). B. Mean firing rate in the experiment and the aEIF model in response to current noise stimulation,...

The effect of dendrites on ISR in Purkinje cells. (DOCX)

ISR in a detailed Purkinje cell model. A. Top, somatic voltage recording from a detailed Purkinje cell model [22] during injection of the noisy current waveform shown at the bottom (similar to the stimulus used in Fig 1A, but with a different range of noise amplitudes). B. Averaged firing frequency (5 simulations) during 1 s noise waveform periods...

Membrane potential distribution during spiking and silent states. A. Membrane potential distributions computed from a somatic whole-cell patch-clamp recording from a Purkinje cell during a stimulus, which evokes transitions between spiking and silent states (Fig 1A). B. Membrane potential distributions in the aEIF model. C. Somatic membrane potenti...

Mutual information and spiking response for high intensity signal input. A. Mutual Information rate of the input and output spike train in the aEIF model when stimulated with 5 Hz signal input. B. Continuous voltage response of the aEIF model when stimulated by 30 pA noise and a Poisson spike train (input amplitude 100 pA, mean frequency 5 Hz, dura...

Experimentally it has been found that around 20% of pyramidal cells in epileptogenic human subiculum do not have KCC2 co-transporter. This pathology leads to the increased chloride level in pyramidal cells, what changes the action of GABA synapses from inhibition to excitation. In this work we propose the single neuron biophysical model to explain...

In this thesis we used dynamical systems methods and numericalsimulations to study the mechanisms of epileptic oscillations associated with ionconcentration changes and cerebellar Purkinje cell bimodal behavior. The general issue in this work is the interplay between single neuron intrinsicproperties and synaptic input structure controlling the neu...

Purkinje cells play an important role in cerebellar computation since their axons are the only projection from the cerebellar cortex to deeper cerebellar structures. They have complex internal dynamics, which allow them to fire spontaneously, display bistability and participate in network phenomena such as high frequency oscillations and travelling...

Purkinje cells play an important role in cerebellar computation since their axons are the only projection from the cerebellar cortex to deeper cerebellar structures. They have complex internal dynamics, which allow them to fire spontaneously, display bistability and participate in network phenomena such as high frequency oscillations and travelling...

Epilepsy is one of the most common neurological disorders. Seizures in about 40% of patients with temporal lobe epilepsies are pharmaco-resistant [1]. In surgically removed hippocampal tissue from these patients, the KCC2 cotransporter is absent or non-functional in about 20 % of subicular pyramidal cells [2]. KCC2 normally assures the maintenance...

Abnormal synchronization of neurons is characteristic for the central nervous system in various neurological diseases, particularly in epilepsy. To describe the dynamics of neurons and to identify causes of this behavior it is necessary to use various theoretical models of individual neurons and populations of cells. In this work we present the pop...

Experimental data reveal the bimodal behavior of Purkinje cells which could be characterized by firing-rate hysteresis in response to current ramp. We propose an adaptive Exponential Integrate-and-Fire neuron (aEIF) model to explain this bimodality. Another phenomenon found in Purkinje cells, inhibition by noise stimuli, so-called Inverse Stochasti...

A firing rate (FR) model for a population of adaptive integrate-and-fire (IF) neurons has been proposed. Unlike known FR models, it describes more precisely the unsteady firing regimes and takes into account the effect of slow potassium currents of spike-time adaptation. Approximations of the adaptive channel conductances are rewritten from voltage...

Synchronization plays important role in generation of brain activity patterns. Experimental data show that neurons demonstrate more reproducible activity for noise-like input than for constant current injection, and that effect can not be reproduced by standard oversimplified Firing-Rate (FR) models. The paper proposes a modification of FR model wh...

Purkinje neurons play an important role in Cerebellar computation. Their axons are the only projection from the cerebellar cortex to deeper cerebellar structures. These neurons appear to have a type II excitability, which can be revealed by a discontinuity in their F-I curves. This intrinsic membrane property of the Purkinje cells implies bistable...

It's well known that synchronous activity play important role in generation of quasiperiodic patterns of brain activity. The imitation of the synaptic current by constant shape signal doesn't always lead to reproducible behavior of one neuron for a long time. But the stimulation by noise-like complex shape signal with fixed parameters lead to the l...

It is well known that synchronous activity play an important role in generation of patterns of brain activity. It has been shown in experimental studies of synchronous activity that neurons demonstrate more reproducible behavior in a response to complex stimuli rather than to constant current injection. In this work we reproduce such experimental r...